Profound effects of electrolyte ions are observed on the kinetics and equilibria of DNA-protein interactions and DNA conformational changes. To understand the molecular and thermodynamic basis of these electrolyte effects, we propose to examine the equilibrium and dynamic behavior of ions and oligocation ligands in the vicinity of DNA, using quadrupolar cation NMR, Monte Carlo (MC) and analytical polyelectrolyte theories, and thermodynamic studies. We propose to obtain accurate descriptions of 1) the steep gradients in electrolyte ion concentrations in the vicinity of the DNA, 2) the local concentration and dynamic behavior of cations at the DNA surface, and 3) the thermodynamic consequences of the changes in these ion gradients that occur when the surface charge density of DNA is altered by conformational changes or by the binding of charged ligands, including proteins. Theoretical and experimental studies will be performed on polymeric DNA and on oligomers of defined chain length and sequences. Monte Carlo studies will be used to define the effects of experimental and modeling parameters on the details of the ion distribution as a function of oligomer chain length, and for the polymer limit. Quadrupolar NMR studies on suitable univalent cations will be performed to check MC predictions for the cation concentration at or near the DNA surface, and to explore the dynamics of these territorially bound ions. Thermodynamic functions and colligative coefficients for the polyelectrolyte solution will be obtained from MC ion distributions and compared with the results of the analytical polyelectrolyte theories. In particular, the polyelectrolyte-electrolyte preferential interaction parameter will be determined, and used in the analysis of electrolyte effects on the ligand-binding reactions and conformational equilibria of DNA. Small ions play a stoichiometric role as effectors or regulators of the equilibria and kinetics of the noncovalent interactions of biopolyelectrolytes in vitro. We propose to survey the range of mechanisms of stoichiometric regulation by small ions, and to examine the relevance of these mechanisms to the regulation of biopolyelectrolyte interactions in vivo, especially in eucaryotic cells where significant variations in intracellular ion concentrations have been observed during the cell cycle and in differentiation.